When animals are chronically exposed to different trace metals, each metal produces a biological response profile which specifically characterizes exposure to that metal. It is the objective of these studies to assess and characterize response profiles based on a thorough understanding of subcellular mechanisms of metal toxicity and specifically to (1) define and correlate ultrastructural and biochemical responses in vivo which characterize exposure to toxic trace elements following chronic exposure and (2) develop early, specific, and sensitive, biochemical testing procedures that may be used to evaluate human populations exposed in utero or as adults to environmentally important toxic elements. Specific metals and areas of interest include the biochemical effects of methyl mercury, cadmium, arsenic, selenium, lead, and lead plus cadmium and arsenic on mitochondrial structure and function. Enzyme activities associated with mitochondrial membranes have been found to show early and pronounced changes in mitochondria of rats and mice following chronic exposure to methyl mercury and arsenic. Further development of these biochemical response profiles should permit development of metal-specific biochemical testing procedures which accurately assess a biological response to these agents prior to overt toxicity. BIBLIOGRAPHIC REFERENCES: Fowler, B.A. and Woods, J.S.: The transplacental toxicity of methyl mercury to fetal rat liver mitochondria: Morphometric and biochemical studies. Lab. Invest. 36: 122-130, February, 1977. Fowler, B.A.: The Toxicology of Environmental Arsenic. In Mehlman, M. and Goyer, R.A. (eds.): Advances in Modern Toxicology III. The Trace Metals. Horizon Publishing Co., 1977, pp 79-122.